Over the past 18 yrs, my laboratory has been investigating human IgE immunoregulation through an in vitro culture system. Our studies using in vitro cultures of blood MNC to study human IgE synthesis induced by recombinant human interleukin 4 (IL-4) have resulted in the development of a highly useful system. The proposed studies will continue to evaluate the usefulness of this system to investigate the regulation of IgE synthesis in normal and hyper IgE states, such as atopy, using IL-4, IL-13, IL-7, IL-10, IL-15, IL-12, IFN(, anti-CD40 and other reagents that have shown promise in this regard.These studies include: 1) the establishment of alloreactive, auto-reactive and antigen-specific T helper cell clones (some of which can trigger normal B cell IgE synthesis) and Epstein-Barr virus-transformed B cell lines which will be used to stimulate and maintain the T cell clones; 2) studies of normal and atopic B cell IgE synthesis when cultured with such clones or purified fresh T cells; with or without the addition of IL-4, IL-13, IL-7, IL-10, IL-15, IL-12, IFN(, anti-CD40 and other mAb's.